Intraoperative Neurophysiological Monitoring in Brain Tumor Surgery: Prospective Cohort Studies

Intraoperative Monitoring of Motor, Visual and Cortico-cortical Evoked Potentials in Brain Tumor Surgery Under General Anesthesia: Prospective Cohort Studies

BACKGROUND Brain tumor surgery requires balancing two competing priorities: maximizing the extent of tumor resection to improve survival while preserving neurological function. This is particularly challenging in eloquent brain tumor surgery, where even minor injury may result in permanent loss of functions such as muscle paralysis, language impairment, or visual loss, substantially affecting patients' independence and quality of life.

Intraoperative neurophysiological monitoring (IOM) combines functional mapping to identify eloquent structures with continuous monitoring of the integrity of eloquent structures during tumor resection. IOM with motor evoked potentials (MEP) is widely used to map and monitor motor-eloquent structurse but still lack high-quality evidence demonstrating patient-related benefit. Other modalities, including cortico-cortical evoked potentials (CCEP) for language monitoring and visual evoked potentials (VEP) for visual pathway monitoring, are promising but lack standardization and further clinical validation.

AIM To strenghten the evidence base and clinical application of IOM in eloquent brain tumor surgery, enabling safer and more effective surgical treatment.

HYPOTHESES

The project is based on the following hypotheses:

1. CCEP monitoring lacks standardization and clinical validation, and its use varies considerably across clinical practice.
2. Intraoperative CCEP signal changes are associated with postoperative language impairment and can be used to establish clinically relevant warning thresholds.
3. IOM with MEP improves motor function preservation and/or increases the extent of safe tumor resection compared with surgery without IOM.
4. Intraoperative VEP signal changes are associated with postoperative visual impairment and can be used to establish clinically relevant warning thresholds.

PROJECT DESIGN The project comprises four unprecedented studies. Part 1 is a scoping review on CCEP monitoring to evaluate current clinical practice and evidence gaps.

Part 2 is a prospective observational cohort study including adult patients undergoing resection of language-eloquent brain tumors in either general anesthesia or asleep-awake-asleep setting which evaluates the association between intraoperative CCEP signal changes and postoperative language impairment, and explores clinically relevant warning thresholds.

Part 3 is a randomized controlled trial in adult patients undergoing resection of motor-eloquent brain tumors which compares surgery performed using IOM with MEP versus no IOM to evaluate its effect on postoperative motor function and extent of tumor resection.

Part 4 is a prospective observational cohort study including adult patients undergoing visual-eloquent transsphenoidal or transcranial surgery for tumors involving the visual pathways. It evaluates the association between intraoperative VEP signal changes and postoperative visual impairment, and explores clinically relevant warning thresholds.

Standardized clinical assessments, advanced neuroimaging, and appropriate statistical analyses will be used for this purpose.

LIMITATIONS Variability between patients, tumor characteristics, and surgical procedures may complicate interpretation of intraoperative signals. In particular, VEP recordings may be affected by physiological and technical variability. Furthermore, ethical and safety considerations mean that not all patients will be eligible for every part of the project.

EXPECTED OUTCOME AND IMPACT Brain tumors are associated with substantial morbidity, permanent loss of function, and mortality. Even modest improvements in functional preservation and the extent of safe tumor resection may significantly improve survival, independence, quality of life, and return to daily activities.

The project is expected to generate unprecedented clinical evidence on IOM in eloquent brain tumor surgery through the first randomized controlled trial evaluating the patient-related benefits of IOM with MEP, and the first prospective studies on CCEP monitoring in awake and general anesthesia setting and VEP monitoring of the entire visual pathway. By addressing major evidence gaps, the project will strengthen the evidence base for IOM, improve interpretation of IOM signals and surgical decision-making, and support rapid implementation into clinical practice locally as well as impacting the use of IOM world wide.

Ultimately, the project is expected to enable safer and more effective brain tumor surgery with a lower risk of permanent motor, language, and visual impairment, improved survival and quality of life, and reduced need for rehabilitation and supportive care, thereby improving patient safety and enabling more precise and effective surgical treatment.

Furthermore, the project is related to the 3rd United Nations sustainable development goal: "Ensure healthy lives and promote well-being for all at all ages."

Study Overview

• Status: Not yet recruiting
• Conditions: Intraoperative Neurophysiological Monitoring; Motor Evoked Potential Monitoring; Malignant Brain Tumors; Cortico-cortical Evoked Potential Monitoring; Visual Evoked Potential Monitoring
• Intervention / Treatment: Diagnostic test: Intraoperative neurophysiological monitoring; Procedure: no Intraoperative neurophysiological monitoring

Detailed Description

BACKGROUND Brain tumor surgery requires balancing two competing priorities: maximizing the extent of tumor resection (EOR) while preserving neurological function to reach maximal safe resection. This balance is particularly challenging in eloquent brain areas, where even minor injuries may result in permanent loss of function such as muscle paralysis, language impairment, or visual loss.

Intraoperative neurophysiological monitoring (IOM) combines functional mapping to identify eloquent structures with continuous monitoring of their integrity during tumor resection. IOM with motor evoked potentials (MEP) is widely used during surgery in general anesthesia or asleep-awake-asleep setting to localize and monitor the precentral gyrus (motor cortex) and corticospinal tract (CST). Continuous stimulation of the precentral gyrus monitors CST integrity throughout resection, while subcortical motor mapping within the resection cavity estimates the distance to the CST and guides the extent of safe resection. Significant warning criteria include a >50% reduction in MEP amplitude or a 20% increase in stimulation threshold, while lower subcortical stimulation thresholds indicate increasing proximity to the CST (approximately 1 mA=1 mm). A subcortical resection limit of 3 mA is usual although lower thresholds can be safe. Combined with diffusion tensor imaging (DTI), MEP monitoring has retrospectively been associated with greater extent of resection and improved long-term survival. Although widely adopted, high-quality evidence demonstrating patient-related benefit remains lacking.

IOM with CCEP is promising for language-eloquent brain tumor surgery and has been studied in general anesthesia and asleep-awake-asleep settings. Direct cortical stimulation of one language area (Broca's or Wernicke's area) with recording from the other enables monitoring of subcortical language tract function, including the arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF). During surgery in asleep-awake-asleep setting, CCEP monitoring complements cortical and subcortical language mapping which temporarily disrupts the patients' speech ability, looking for speech arrest and phonological paraphasia which is linked to AF function disruption. CCEP waveforms comprise positive (P1, P2) and negative (N1, N2) deflections. A previous study by Seidel et al. (co-applicant) demonstrated an association between N2 latency changes during awake surgery and postoperative language impairment. However, it remains unclear whether amplitudes, latencies, or both provide the most clinically relevant information, and validated warning thresholds have yet to be established. Consequently, IOM with CCEP lacks standardization and further clinical validation.

IOM with VEP can be used to monitor visual pathway function during visual-eloquent surgery. The visual pathways are normally divided into the anterior (structures from the retina to the lateral geniculate body) and posterior visual pathways (from the lateral geniculate body to the primary visual cortex). Flash stimulation delivered through light-emitting diode eye pads evoke cortical responses recorded using scalp electroencephalography (EEG), and when applicable, strip electrodes placed over the visual cortex to improve signal quality. Simultaneous electroretinography confirms adequate retinal light stimulation. Previous studies have demonstrated promising results for preserving anterior visual pathway function during prechiasmal and sellar/suprasellar tumor surgery, including endoscopic transsphenoidal surgery. However, evidence for monitoring posterior visual pathway function remains limited. Furthermore, considerable intra- and interindividual variability and signal instability reduces signal reliability and limits clinical applicability to patients with sufficient baseline visual function. VEP waveforms comprise an initial deflection called N1 and a prominent deflection called P100 (also known as P2). Focus has been on the voltage difference between N1 and P2 (P100) on one hand, and P100 amplitude on the other hand. Although a 50% reduction in the N1-P2 peak-to-peak amplitude has been proposed as a warning criterion, clinically relevant VEP signal changes and validated warning thresholds remain uncertain. Consequently, IOM with VEP lacks standardization and further clinical validation and is therefore not widely adopted.

PURPOSE

The overall aim is to strengthen the evidence base supporting the standardization and clinical application of IOM in eloquent brain tumor surgery. The project comprises four unprecedented studies (Parts 1-4) with the following objectives:

1. To evaluate current clinical practice and evidence gaps in cortico-cortical evoked potential (CCEP) monitoring.
2. To evaluate the clinical significance of CCEP monitoring by assessing the association between intraoperative signal changes and postoperative language outcomes, and to explore clinically relevant warning thresholds.
3. To evaluate the clinical effectiveness of IOM with motor evoked potentials (MEP) compared with surgery without IOM.
4. To evaluate the clinical significance of VEP monitoring by assessing the association between intraoperative signal changes and postoperative visual outcomes, and to explore clinically relevant warning thresholds.

HYPOTHESIS

1. CCEP monitoring lacks standardization and clinical validation, and its use varies considerably across clinical practice.
2. Intraoperative CCEP signal changes are associated with postoperative language impairment and can be used to establish clinically relevant warning thresholds.
3. IOM with MEP improves motor function preservation and/or increases the extent of safe tumor resection compared with surgery without IOM.

4. Intraoperative VEP signal changes are associated with postoperative visual impairment and can be used to establish clinically relevant warning thresholds.

   METHODS Patients scheduled for brain tumor surgery at Odense University Hospital will be screened for eligibility according to the inclusion criteria for each clinical study (Parts 2-4) and recruited during routine outpatient assessment.

   Part 1: Intraoperative neurophysiological monitoring with cortico-cortical evoked potentials (CCEP) during language-eloquent intracranial surgery: A scoping review

   Aim: To systematically review the literature on intraoperative CCEP monitoring in brain surgery to identify current clinical practices, methodological variability, and remaining knowledge gaps that may guide future research and clinical implementation.

   Methods: A scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. PubMed will be systematically searched using terms including "cortico-cortical evoked potential", "CCEP", and "intraoperative". Eligible studies will be reviewed to evaluate: 1) Clinical applications of intraoperative CCEP monitoring; 2) Proposed warning thresholds; 3) Use during surgery in general anesthesia; 4) Integration with preoperative imaging; 5) Pre- and postoperative language assessment; 6) Patient outcome assessment methods.

   Part 2: Intraoperative neurophysiological monitoring with cortico-cortical evoked potentials (CCEP) during surgical resections of language-eloquent brain tumors: A prospective observational cohort study

   Aim: To prospectively evaluate the association between intraoperative CCEP signal changes and postoperative language impairment in patients undergoing language-eloquent brain tumor surgery in either general anesthesia or asleep-awake-asleep setting, and to explore clinically relevant warning thresholds that support safe tumor resection while preserving language function.

   Methods:

   Preoperative contrast-enhanced MRI combined with DTI will be used to determine tumor location relative to language-eloquent areas. Baseline language function will be assessed using validated language tests (e.g. the DuLIP language test battery and the Western Aphasia Battery). Patients scheduled for surgery in asleep-awake-asleep setting will additionally undergo neuropsychological assessment and training for intraoperative language testing.

   During surgery in general anesthesia, Broca's and Wernicke's areas will be identified intraoperative using preoperative imaging and anatomical landmarks. Strip electrodes will be placed over the presumed Broca's and Wernicke's areas, with stimulation of Broca's area and recording from Wernicke's area (BtW-asleep). CCEP recordings will be obtained using two adjacent electrodes, two repeated trials of 30-60 averaged responses, and continuous bipolar and referential monitoring. A valid CCEP will be defined by the presence of distinct P1 and N1 waveforms. Amplitudes and peak latencies of P1, N1, P2 and N2 will be monitored throughout surgery.

   During surgery in asleep-awake-asleep setting, cortical mapping with bipolar Penfield language mapping will additionally be performed in the awake phase to identify a safe cortical entry site. Stimulation will be increased from 2 mA in 1 mA increments until speech arrest is elicited without afterdischarges on electrocorticography, after which the same stimulation intensity (typically 3-6 mA) will be used for further cortical language mapping.

   CCEP monitoring (BtW-awake) will be initiated immediately after cortical Penfield language mapping, preferably before cortical incision, and continued throughout the subsequent asleep phase as described above. Subcortical language mapping will be performed to guide tumor resection in the awake phase using monopolar probe stimulation within the resection cavity to localize language eloquent structures and estimate their distance from the resection margin. The stimulation intensity identified during cortical language mapping will be used, and speech arrest or phonological paraphasia will guide cessation of tumor resection at the corresponding site.

   Statistical analyses for this observational study will compare the difference in mean value of CCEP amplitude, latency and stimulation threshold changes from baseline between patients with and without postoperative language impairment/worsening of language impairment at 1- and 3-month follow-up. Between-group comparisons will be performed using two-sample t-test (two-sided) or Mann-Whitney U test, depending on data distribution. Adjusted logistic regression models will be fitted including EOR and histopathologic diagnosis, and Receiver Operating Characteristic and Area Under the Curve (ROC/AUC) and diagnostic accuracy measures will be computed. Clinically relevant warning thresholds will be explored as the greatest amplitude reduction, latency prolongation, or stimulation threshold increase not associated with significant postoperative language impairment.

   Sample Size calculations are based on Welch's two-sample t-test corresponding to the comparison of mean N2 latency during resection between patients with and without aphasia. Assumed effect sizes are based on observations from Seidel et al., which recorded N2 latency to be 64.0 ± 12.6ms (mean ±SD) in patients with postoperative aphasia and 48.8 ± 14.2ms in patients without aphasia. The study included 19 patients out of which 7 (i.e. 36.8%) had postoperative aphasia. The observational nature of the grouping variable causes random group sizes and corresponding additional variation is considered for sample size calculations using the approach of Ambrosius et al. The latter considers both the uncertainty in the population group ratio (i.e. the 36.8%) as well as the future realized group allocation. For the parameters θ1and θ2 of the Beta prior we have chosen the values 7.5 and 12.5 which corresponds to the posterior parameters obtained after updating a Jeffrey's prior with data from the study (i.e. 7 vs. 12 patients with/without aphasia). The resulting required sample size corresponding to a significance level of 0.05 and an expected power of 0.8 is N=33 patients. Other clinically relevant secondary outcomes are not used to determine sample size and will be considered explorative or descriptive.

   Part 3: Intraoperative neurophysiological monitoring (IOM) with motor evoked potentials (MEP) versus no IOM during surgical resections motor-eloquent brain tumors: A randomized controlled trial

   Aim: To prospectively evaluate the effect of IOM with MEP on postoperative motor function and extent of tumor resection (EOR) compared with surgery without IOM in patients undergoing motor-eloquent brain tumor surgery in general anesthesia setting.

   Methods:

   Patients undergoing resection of motor-eloquent brain tumors will be randomized in a 1:1 ratio assigned to surgery with or without IOM (IOM or no IOM). Allocation will be concealed using a computer-generated block randomization sequence with variable block sizes. Patients at highest risk of function loss (direct tumor involvement of motor-eloquent structures) will be excluded and treated using IOM.

   Preoperative contrast-enhanced MRI combined with DTI and functional MRI will be used to determine tumor location relative to motor-eloquent structures1. Motor function will be assessed using the Medical Research Council (MRC) scale, National Institutes of Health Stroke Scale (NIHSS) motor subscore, Six-Spot-Step Test (SSST), 9-Hole Peg Test (NHPT), hand dynamometry, and 10-Meter Walk Test (10MWT). Overall functional status will be assessed using the Karnofsky Performance Scale (KPS).

   During surgery without IOM, the precentral gyrus, CST, and a safe incision zone will be identified intraoperative using preoperative imaging studies, anatomical landmarks, and navigated intraoperative ultrasonography in all patients. During surgery with IOM, cortical mapping will additionally be performed using monopolar probe stimulation.

   Durin surgery with IOM, MEP monitoring of CST integrity will be with direct cortical stimulation and transcranial stimulation with scalp electrodes. A >50% reduction in MEP amplitude or a 20% increase in stimulus threshold will be considered significant warning criteria and guide cessation of tumor resection at the specific site. Subcortical motor mapping of the CST will be performed using monopolar probe stimulation within the resection cavity, initially at 10-15 mA and gradually reduced as resection approaches the CST. An MEP threshold of 3 mA will guide cessation of tumor resection at the specific site, subject to the surgeon's assessment (critical threshold: 1 mA).

   Statistical analyses will compare the primary outcome (MRC sum score) between treatment groups (IOM vs. no IOM) using independent two-sample t-tests or Mann-Whitney U tests, as appropriate. Treatment effects will be reported as mean differences with 95% confidence intervals and standardized effect sizes. Adjusted analyses will be performed using linear regression (ANCOVA) including baseline MRC score, age, tumor volume, distance to the corticospinal tract, and histopathological diagnosis as prespecified covariates.

   Key secondary outcomes are not individually powered and will be analysed using the same two-stage approach of unadjusted group comparisons followed by adjusted linear regression models and interpreted as supportive evidence.

   Longitudinal primary and key secondary outcomes will additionally be analysed using linear mixed-effects models including fixed effects for treatment, time, and treatment-by-time interaction, and a random intercept for participant.

   Ordinal exploratory secondary outcomes (Engel seizure classification, PGIC, and Surgeon-rated usefulness) will be analysed using ordinal logistic regression or rank-based tests. Binary exploratory outcomes (completeness of fluorescein-guided tumor resection and tumor progression) will be analysed using chi-square or Fisher´s exact tests, with generalized linear models used to estimate relative risks with 95% confidence intervals. Time to tumor progression will additionally be explored using Kaplan-Meier curves and Cox proportional hazards regression.

   Safety endpoints will be summarized descriptively by treatment group. All tests will be two-sided with a significance level of α=0.05 for the primary outcome. Secondary and exploratory outcomes will be interpreted primarily using effect estimates and 95% confidence intervals.

   Sample size calculations indicate that n=66 participants (33 per group) are required to detect a clinically meaningful difference in postoperative motor function assuming a standard deviation of 1.0 on the MRC score and a conservative literature-supported standardized mean difference of Cohen's d=0.704 for continuous motor outcome, with a two-sided significance level of α=0.05 and 80% power. As this kind of randomized controlled trial is unprecedented, these assumptions are intentionally conservative. Secondary outcomes and safety endpoints are not included in the sample size calculation and will be analysed as supportive, exploratory, or descriptive outcomes.

   Part 4: Intraoperative signal changes of visual evoked potentials (VEP) during transsphenoidal and transcranial tumor resections: Clinical correlation and warning thresholds

   Aim: To prospectively evaluate the association between intraoperative VEP signal changes and postoperative visual impairment in patients undergoing visual-eloquent transsphenoidal pituitary tumor or transcranial brain tumor surgery in general anesthesia setting, and to explore clinically relevant warning thresholds that support safe tumor resection while preserving visual function.

   Methods:

   Preoperative contrast-enhanced MRI combined with DTI will be used to determine tumor location relative to the visual pathways. Visual function will be assessed by best-corrected visual acuity and perimetry.

   Intraoperative binocular flash stimulation will be delivered using light-emitting diode eye pads placed over the closed eyelids and secured with a protective seal. Flash visual evoked potentials will be recorded using low amplitude scalp EEG over the occipital lobes and simultaneous electroretinography to confirm adequate retinal light stimulation. During transcranial surgery, a strip electrode will additionally be placed over the occipital cortex when permitted by the craniotomy, locating the visual cortex with the use of preoperative imaging and adjusting electrode placement to optimize VEP recordings. Stimulation intensity will be 7,000-8,000 lx with alternating light-on and light-off stimulation.

   VEP monitoring will be performed by continuous flash stimulation with monitoring of N1 and P2 (P100) amplitudes and latencies using low amplitude scalp EEG, and strip electrodes when applicable.

   Statistical analyses for this observational study will compare the difference in mean value of VEP amplitude, N1-P2 peak-to-peak amplitude, and VEP latency changes from baseline between patients with and without postoperative visual impairment/worsening of visual impairment at 1-2 weeks and 3 months. Between-group comparisons will be performed using two-sample t-test (two-sided) or Mann-Whitney U test, depending on data distribution. Adjusted logistic regression models will be fitted including EOR, and ROC/AUC and diagnostic accuracy measures will be computed. Clinically relevant warning thresholds will be explored as the greatest VEP or N1-P2 peak-to-peak amplitude reduction or VEP latency prolongation not associated with significant postoperative visual impairment.

   Sample Size calculations indicate that n=64 participants are required to detect the expected difference in the incidence of VEP signal changes associated with postoperative visual impairment compared with those not associated with visual impairment (9.4% vs. 56.3%, two-sample proportion test, two-sided α=0.05, power 0.8).

   EXPECTED OUTCOME AND IMPACT Brain tumors are associated with substantial morbidity, permanent loss of function, and mortality. Even modest improvements in functional preservation and the extent of safe tumor resection may significantly improve survival, independence, quality of life, and return to daily activities.

   The project is expected to generate unprecedented clinical evidence on IOM in eloquent brain tumor surgery through the first randomized controlled trial evaluating the patient-related benefits of IOM with MEP, and the first prospective studies on CCEP monitoring in awake and general anesthesia setting and VEP monitoring of the entire visual pathway. By addressing major evidence gaps, the project will strengthen the evidence base for IOM, improve interpretation of IOM signals and surgical decision-making, and support rapid implementation into clinical practice locally as well as impacting the use of IOM world wide.

   Ultimately, the project is expected to enable safer and more effective brain tumor surgery with a lower risk of permanent motor, language, and visual impairment, improved survival and quality of life, and reduced need for rehabilitation and supportive care, thereby improving patient safety and enabling more precise and effective surgical treatment.

   Furthermore, the project is related to the 3rd United Nations sustainable development goal: "Ensure healthy lives and promote well-being for all at all ages."

   FEASIBILITY AND COLLABORATIONS A multidisciplinary collaboration is well established between the Departments of Neurosurgery and Clinical Neurophysiology at Odense University Hospital (OUH) and Professor Kathleen Seidel who is an internationally recognized expert in IOM.

   Our department has extensive experience with IOM, access to a large and relevant patient population, and a strong research infrastructure, facilitating both project completion and early clinical implementation.

   Parts 2 and 4 are prospective observational studies, enabling early data acquisition and statistical model development. Based on our patient volume, we expect to recruit 25 patients/year for Part 2 (n = 33), 20-25 patients/year for Part 3 (n = 66), and 48 patients/year for Part 4 (n = 64). The sample size for Part 3 is based on conservative literature-supported assumptions, and a larger treatment effect may reduce the required sample size. Overall, the project is considered highly feasible within the planned three-year timeframe.

   DATA MANAGEMENT, SHARING AND DISSEMINATION A Research Electronic Data Capture database will be used for safe data storage, OPEN Analyze for statistical data storage, and Stata IC for analysis. All systems are hosted by OPEN on secure servers in the Region of Southern Denmark (RSYD). The project will be registered in RSYD´s record of Data Processing Activities and conducted in accordance with the EU General Data Protection Regulation (GDPR), the Danish Data Protection Act, the Danish Health Act, and Good Clinical Practice standard.

   All project data will be made available through Zenodo open data repository. Results will be published in international peer-reviewed Open Access journals and presented at national and international conferences. Lay summaries will be disseminated through patient organizations, including the Danish Brain Tumor Association, and presented to ensure broad accessibility for both healthcare professionals and the public.

   ROLES Dr. Grønhøj (Principal Applicant): Overall responsibility for project management, administration, and coordination. Performs surgeries, oversees patient recruitment and follow-up, and supervises the PhD student in funding acquisition, data curation, statistical analyses, patient and public involvement, and manuscript preparation.

   Björnsson, MD (PhD student): Responsible for protocol development, funding acquisition, project coordination, patient recruitment and follow-up, data curation, statistical analyses, scientific and public dissemination, and manuscript preparation, all under supervision.

   Dr. Binzer (Co-applicant): Performs intraoperative monitoring and supervises patient recruitment, funding acquisition, data curation, statistical analyses, and manuscript preparation.

   Prof. Seidel (Co-applicant): Contributes to data interpretation, scientific discussion, and manuscript preparation, and supervises the PhD student during a two-week research stay in Bern.

   PERMITS The project proposal has been approved as the basis for PhD enrolment at the Graduate School of Health Sciences, SDU, and Björnsson has been accepted as the PhD candidate. Ethical approval has been submitted to the Danish National Committee on Health Research Ethics and is currently under review.

   ABBREVIATIONS EOR: extent of tumor resection IOM: Intraoperative neurophysiological monitoring MEP: motor evoked potentials CST: corticospinal tract DTI: diffuse tension imaging CCEP: cortico-cortical evoked potentials VEP: visual evoked potentials AF: arcuate fasciculus SLF: superior longitudinal fasciculus EEG: electroencephalography PRISMA-ScR: Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews mA: milliampere MRI: magnetic resonance imaging DuLIP: the Dutch Linguistic Intraoperative Protocol BtW: Broca to Wernicke μV: microvolts ms: milliseconds ROC/AUC: Receiver Operating Characteristic and Area Under the Curve SD: standard deviation MRC: Medical Research Council NIHSS: the National Institutes of Health Stroke Scale ANCOVA: Analysis of Covariance lx: Lux OUH: Odense University Hospital RSYD: Region of Southern Denmark MD: Medical doctor

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Einar T Björnsson, Medical Doctor; Phone Number: +45 50 65 80 79; Email: einar.teitur.bjornsson@rsyd.dk
• Study Contact Backup: Name: Mads H Grønhøj, Medical Doctor, PhD; Phone Number: +45 23 25 27 38; Email: mads.groenhoej@rsyd.dk

Study Locations

• Denmark
  • Fyn
    • Odense, Fyn, Denmark, 5000
      • Department of Neurosurgery, Odense University Hospital
      • Contact: Einar T Björnsson, Medical Doctor; Phone Number: +45 50 65 80 79; Email: einar.teitur.bjornsson@rsyd.dk
      • Contact: Mads H Grønhøj, Associate Professor; Phone Number: +45 23 25 27 38; Email: mads.hjortdal.groenhoej@rsyd.dk
      • Principal Investigator: Einar T Björnsson, Medical Doctor
      • Sub-Investigator: Stefanie Binzer, Medical Doctor, PhD
      • Sub-Investigator: Kathleen Seidel, Medical Doctor, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Part 1 is a litterature review.

Part 2 - Inclusion Criteria:

1. Patient age ≥ 18 years and ability to provide informed consent;
2. Planned resection of ≥ 1 contrast-enhancing brain tumors (tentative diagnosis high-grade glioma or metastasis) on magnetic resonance imaging (MRI) in either general anesthesia or asleep-awake-asleep setting;
3. Intended gross total or complete tumor resection;
4. Tumor located < 10 mm from the language areas (Broca's or Wernicke's) or subcortical language tracts (AF or SLF);
5. Tumor located in a language-dominant hemisphere;
6. Written informed consent.

Part 2 - Exclusion Criteria:

1. Tumors directly involving Broca's or Wernicke's area;
2. Pregnancy;
3. Emergency surgery;
4. Tumors involving both hemispheres.

Part 3 - Inclusion Criteria:

1. Patient age ≥ 18 years and ability to provide informed consent;
2. Planned resection of ≥ 1 contrast enhancing brain tumors (tentative diagnosis high-grade glioma or metastasis) on MRI in general anesthesia setting;
3. Intended gross total or complete tumor resection;
4. Tumor located < 20 mm from the precentral gyrus or CST;
5. Written informed consent.

Part 3 - Exclusion Criteria:

1. Tumors directly involving the precentral gyrus or CST;
2. Pregnancy;
3. Emergency surgery;
4. Recurrent brain tumor surgery;
5. Tumors involving both hemispheres.

Part 4 - Inclusion Criteria:

1. Patient age ≥ 18 years and ability to provide informed consent;
2. Planned resection of ≥ 1 contrast enhancing pituitary tumors (tentative diagnosis adenoma), contrast enhancing brain tumors (tentative diagnosis high-grade glioma, metastasis or meningioma), or non-enhancing brain tumors (tentative diagnosis low-grade glioma) on MRI in general anesthesia setting;
3. Intended gross total or complete tumor resection;
4. Tumor located < 10 mm from, or involving, the anterior or posterior visual pathways;
5. Written informed consent.

Part 4 - Exclusion Criteria:

1. Pregnancy;
2. Emergency surgery;
3. Severe visual impairment precluding reliable VEP monitoring (typically best-corrected visual acuity ≤ 0.2-0.4 on the Snellen scale).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IOM with MEP; Patients undergoing brain tumor surgery randomized to IOM with MEP	Diagnostic test: Intraoperative neurophysiological monitoring; The project includes three clinical studies: Part 2 is an observational cohort which includes patients planned for resection of a speech eloquent brain tumor. Intraoperative monitoring with cortico-cortical evoked potentials (CCEP) will be performed with the aim of exploring the relation of CCEP signal changes and postoperative speech impairment. Part 3 is a randomized controlled trial which includes patients planned for resection of a motor eloquent brain tumor. Patients randomized to surgery with intraoperative monitoring (IOM) will undergo surgery using IOM with motor evoked potentials (MEP). Part 4 is an observational cohort which includes patients planned for resection of a visual eloquent brain tumor. Intraoperative monitoring with visual evoked potentials (VEP) will be performed with the aim of exploring the relation of VEP signal changes and postoperative speech impairment.; Other Names: IOM
Active Comparator: no IOM; Patients undergoing brain tumor surgery randomized to no IOM	Procedure: no Intraoperative neurophysiological monitoring; Part 3 is a randomized controlled trial which includes patients planned for resection of a motor eloquent brain tumor. Patients randomized to surgery with no intraoperative monitoring (IOM) will undergo surgery without IOM with motor evoked potentials (MEP).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CCEP signal changes	Changes in CCEP amplitudes of P1, N1, P2, N2 (μV and %) and peak latencies (ms and %), and stimulation threshold (mA and %) relative to baseline (BtW-asleep and BtW-awake)	Intraoperative
Postoperative language function	Postoperative language function assessed using the DuLIP language test battery and Western Aphasia Battery at approximately 1 month, and again at 3 months in patients with speech impairment at at the 1-month follow-up. Significant speech impairment is defined as a deterioration of ≥ 2 points on the DuLIP language test battery and/or ≥ 5 points or a change in aphasia severity category on Western Aphasia Battery)	At 1 month, and again at 3 months in patients with speech impairment at 1 month
Postoperative motor function	Postoperative motor function using the Medical Research Council scale during admission and at 1-month follow-up (0-5; 0-worse outcome, 5-better outcome).	Postoperative Day 1, and at 1-month follow-up
VEP signal changes	Changes in VEP amplitudes of N1, P2 (P100), and N1-P2 peak-to-peak (μV and %) and latencies (ms and %) relative to baseline	Intraoperative
Postoperative visual function	Postoperative visual function assessed using best-corrected visual acuity and perimetry. Significant postoperative visual impairment is defined as ≥2-line deterioration on the Snellen scale (total of 11 lines) and/or new or clinically relevant worsening of the visual field (mean deviation or pattern).	At 1-2 weeks and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EOR	Postoperative Extent of tumor resection (absolute and relative tumor volume; %) by MRI	Postoperative Day 1
Karnofsky Performance Scale	Karnofsky Performance Scale score (0-100; 0-worse outcome, 100-better outcome)	At 1-month follow-up
National Institutes of Health Stroke Scale motor subscore	National Institutes of Health Stroke Scale motor subscore (0-8; 0-better outcome, 8-worse outcome)	During admission (Postoperative Day 1), and at 1-month follow-up
Hand dynamometry	Hand dynamometry (kg)	Postoperative Day 1, and at 1-month follow-up
10-Meter Walk Test	10MWT (m/s)	Postoperative Day 1, and at 1-month follow-up
Six-Spot-Step Test	SSST (seconds)	Postoperative Day 1, and at 1-month follow-up
9-Hole Peg Test	NHPT (seconds)	Postoperative Day 1, and at 1-month follow-up
Seizure outcome	Change in Engel classification (I-IV; I-better outcome, IV-worse outcome) or antiepileptic medicine (Improved/unchanged/worsened)	At 1-month follow-up
Patient Global Impression of Change	Patient Global Impression of Change (1-7; 1-better outcome, 7-worse outcome)	At 1-month follow-up
Completeness of fluorescein-guided tumor resection	Completeness of fluorescein-guided tumor resection under the microscope (yes/no)	Intraoperative
Surgeon-rated usefulness	Surgeon-rated usefulness of intraoperative guidance (5-point Likert scale; 1-better outcome, 5-worse outcome)	Intraoperative
Tumor progression	Tumor progression (yes/no)	At 3- and 6-months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality (yes/no)	At 1, 3, and 6 months
Postoperative complications	Postoperative complications (yes/no; e.g. pulmonary embolism, deep venous thrombosis, infection, cerebral infarction, or hemorrhage)	Within 1 month

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Study Director: Mads H Grønhøj, Medical Doctor, PhD, Department of Neurosurgery, Odense University Hospital; Study Chair: Frantz R Poulsen, Medical Doctor, PhD, Professor, Department of Neurosurgery, Odense University Hospital

Publications and helpful links

General Publications

• Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003 May;41(5):582-92. doi: 10.1097/01.MLR.0000062554.74615.4C.
• Macdonald DB, Skinner S, Shils J, Yingling C; American Society of Neurophysiological Monitoring. Intraoperative motor evoked potential monitoring - a position statement by the American Society of Neurophysiological Monitoring. Clin Neurophysiol. 2013 Dec;124(12):2291-316. doi: 10.1016/j.clinph.2013.07.025. Epub 2013 Sep 18.
• Matsumoto R, Nair DR, LaPresto E, Najm I, Bingaman W, Shibasaki H, Luders HO. Functional connectivity in the human language system: a cortico-cortical evoked potential study. Brain. 2004 Oct;127(Pt 10):2316-30. doi: 10.1093/brain/awh246. Epub 2004 Jul 21.
• Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors. J Neurosurg. 2013 Feb;118(2):287-96. doi: 10.3171/2012.10.JNS12895. Epub 2012 Nov 30.
• Raabe A, Beck J, Schucht P, Seidel K. Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method. J Neurosurg. 2014 May;120(5):1015-24. doi: 10.3171/2014.1.JNS13909. Epub 2014 Mar 14.
• Schucht P, Seidel K, Beck J, Murek M, Jilch A, Wiest R, Fung C, Raabe A. Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome. Neurosurg Focus. 2014 Dec;37(6):E16. doi: 10.3171/2014.10.FOCUS14524.
• Jashek-Ahmed F, Cabrilo I, Bal J, Sanders B, Grieve J, Dorward NL, Marcus HJ. Intraoperative monitoring of visual evoked potentials in patients undergoing transsphenoidal surgery for pituitary adenoma: a systematic review. BMC Neurol. 2021 Jul 23;21(1):287. doi: 10.1186/s12883-021-02315-4.
• Chung SB, Park CW, Seo DW, Kong DS, Park SK. Intraoperative visual evoked potential has no association with postoperative visual outcomes in transsphenoidal surgery. Acta Neurochir (Wien). 2012 Aug;154(8):1505-10. doi: 10.1007/s00701-012-1426-x. Epub 2012 Jun 29.
• Sasaki T, Itakura T, Suzuki K, Kasuya H, Munakata R, Muramatsu H, Ichikawa T, Sato T, Endo Y, Sakuma J, Matsumoto M. Intraoperative monitoring of visual evoked potential: introduction of a clinically useful method. J Neurosurg. 2010 Feb;112(2):273-84. doi: 10.3171/2008.9.JNS08451.
• De Witt Hamer PC, Robles SG, Zwinderman AH, Duffau H, Berger MS. Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. J Clin Oncol. 2012 Jul 10;30(20):2559-65. doi: 10.1200/JCO.2011.38.4818. Epub 2012 Apr 23.
• Duffau H, Velut S, Mitchell MC, Gatignol P, Capelle L. Intra-operative mapping of the subcortical visual pathways using direct electrical stimulations. Acta Neurochir (Wien). 2004 Mar;146(3):265-9; discussion 269-70. doi: 10.1007/s00701-003-0199-7. Epub 2004 Jan 8.
• Sato A, Ogiwara T, Sasaki T, Hongo K, Horiuchi T. How should visual function monitoring be performed and interpreted in surgery for suprasellar tumors? J Neurosurg. 2024 Apr 12;141(3):720-729. doi: 10.3171/2024.1.JNS232118. Print 2024 Sep 1.
• Sato A. Interpretation of the causes of instability of flash visual evoked potentials in intraoperative monitoring and proposal of a recording method for reliable functional monitoring of visual evoked potentials using a light-emitting device. J Neurosurg. 2016 Oct;125(4):888-897. doi: 10.3171/2015.10.JNS151228. Epub 2016 Feb 19.
• Houlden DA, Turgeon CA, Polis T, Sinclair J, Coupland S, Bourque P, Corsten M, Kassam A. Intraoperative flash VEPs are reproducible in the presence of low amplitude EEG. J Clin Monit Comput. 2014 Jun;28(3):275-85. doi: 10.1007/s10877-013-9532-8.
• Feng R, Schwartz J, Loewenstern J, Kohli K, Lenina S, Ultakan S, Iloreta AM, Govindaraj S, Bederson J, Banik R, Shrivastava R. The Predictive Role of Intraoperative Visual Evoked Potentials in Visual Improvement After Endoscopic Pituitary Tumor Resection in Large and Complex Tumors: Description and Validation of a Method. World Neurosurg. 2019 Jun;126:e136-e143. doi: 10.1016/j.wneu.2019.01.278. Epub 2019 Feb 19.
• Houlden DA, Turgeon CA, Amyot NS, Edem I, Sinclair J, Agbi C, Polis T, Alkherayf F. Intraoperative Flash Visual Evoked Potential Recording and Relationship to Visual Outcome. Can J Neurol Sci. 2019 May;46(3):295-302. doi: 10.1017/cjn.2019.4. Epub 2019 Mar 14.
• Boex C, Goga C, Berard N, Al Awadhi A, Bartoli A, Meling T, Bijlenga P, Schaller K. Intraoperative subcortico-cortical evoked potentials of the visual pathway under general anesthesia. Clin Neurophysiol. 2021 Jul;132(7):1381-1388. doi: 10.1016/j.clinph.2021.02.399. Epub 2021 Apr 9.
• Gogos AJ, Young JS, Morshed RA, Avalos LN, Noss RS, Villanueva-Meyer JE, Hervey-Jumper SL, Berger MS. Triple motor mapping: transcranial, bipolar, and monopolar mapping for supratentorial glioma resection adjacent to motor pathways. J Neurosurg. 2020 Jun 5;134(6):1728-1737. doi: 10.3171/2020.3.JNS193434. Print 2021 Jun 1.
• Yeole U, Singh V, Mishra A, Shaikh S, Shetty P, Moiyadi A. Navigated intraoperative ultrasonography for brain tumors: a pictorial essay on the technique, its utility, and its benefits in neuro-oncology. Ultrasonography. 2020 Oct;39(4):394-406. doi: 10.14366/usg.20044. Epub 2020 Jun 17.
• Ambrosius WT, Mahnken JD. Power for studies with random group sizes. Stat Med. 2010 May 10;29(10):1137-44. doi: 10.1002/sim.3873.
• Kunieda T, Yamao Y, Kikuchi T, Matsumoto R. New Approach for Exploring Cerebral Functional Connectivity: Review of Cortico-cortical Evoked Potential. Neurol Med Chir (Tokyo). 2015;55(5):374-82. doi: 10.2176/nmc.ra.2014-0388. Epub 2015 Apr 28.
• De Witte E, Satoer D, Robert E, Colle H, Verheyen S, Visch-Brink E, Marien P. The Dutch Linguistic Intraoperative Protocol: a valid linguistic approach to awake brain surgery. Brain Lang. 2015 Jan;140:35-48. doi: 10.1016/j.bandl.2014.10.011. Epub 2014 Dec 17.
• Riva M, Fava E, Gallucci M, Comi A, Casarotti A, Alfiero T, Raneri FA, Pessina F, Bello L. Monopolar high-frequency language mapping: can it help in the surgical management of gliomas? A comparative clinical study. J Neurosurg. 2016 May;124(5):1479-89. doi: 10.3171/2015.4.JNS14333. Epub 2015 Sep 25.
• Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tuncalp O, Straus SE. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018 Oct 2;169(7):467-473. doi: 10.7326/M18-0850. Epub 2018 Sep 4.
• Odom JV, Bach M, Brigell M, Holder GE, McCulloch DL, Mizota A, Tormene AP; International Society for Clinical Electrophysiology of Vision. ISCEV standard for clinical visual evoked potentials: (2016 update). Doc Ophthalmol. 2016 Aug;133(1):1-9. doi: 10.1007/s10633-016-9553-y. Epub 2016 Jul 21.
• Sharma R, Joshi S, Singh KD, Kumar A. Visual Evoked Potentials: Normative Values and Gender Differences. J Clin Diagn Res. 2015 Jul;9(7):CC12-5. doi: 10.7860/JCDR/2015/12764.6181. Epub 2015 Jul 1.
• Nishimura F, Wajima D, Park YS, Motoyama Y, Nakagawa I, Yamada S, Yokota H, Tamura K, Matsuda R, Takeshima Y, Takatani T, Nakase H. Efficacy of the visual evoked potential monitoring in endoscopic transnasal transsphenoidal surgery as a real-time visual function. Neurol India. 2018 Jul-Aug;66(4):1075-1080. doi: 10.4103/0028-3886.236963.
• Luo Y, Regli L, Bozinov O, Sarnthein J. Clinical utility and limitations of intraoperative monitoring of visual evoked potentials. PLoS One. 2015 Mar 24;10(3):e0120525. doi: 10.1371/journal.pone.0120525. eCollection 2015.
• Gutzwiller EM, Cabrilo I, Radovanovic I, Schaller K, Boex C. Intraoperative monitoring with visual evoked potentials for brain surgeries. J Neurosurg. 2018 Mar 30;130(2):654-660. doi: 10.3171/2017.8.JNS171168.
• Ota T, Kawai K, Kamada K, Kin T, Saito N. Intraoperative monitoring of cortically recorded visual response for posterior visual pathway. J Neurosurg. 2010 Feb;112(2):285-94. doi: 10.3171/2009.6.JNS081272.
• Rajashekar D, Lavrador JP, Ghimire P, Keeble H, Harris L, Pereira N, Patel S, Beyh A, Gullan R, Ashkan K, Bhangoo R, Vergani F. Simultaneous Motor and Visual Intraoperative Neuromonitoring in Asleep Parietal Lobe Surgery: Dual Strip Technique. J Pers Med. 2022 Sep 9;12(9):1478. doi: 10.3390/jpm12091478.
• Zauli FM, Revay M, Terzaghi M, Solbiati M, Cassani CM, Cossu M, d'Orio P, Castana L, Cardinale F, Mikulan E, Sartori I. Cortical and subcortical intraoperative-monitoring of the visual pathway under general anesthesia in epilepsy surgery. Clin Neurophysiol. 2024 Oct;166:96-107. doi: 10.1016/j.clinph.2024.07.011. Epub 2024 Jul 26.
• Shahar T, Korn A, Barkay G, Biron T, Hadanny A, Gazit T, Nossek E, Ekstein M, Kesler A, Ram Z. Elaborate mapping of the posterior visual pathway in awake craniotomy. J Neurosurg. 2018 May;128(5):1503-1511. doi: 10.3171/2017.2.JNS162757. Epub 2017 Aug 25.
• COPENHAVER RM, BEINHOCKER GD. EVOKED OCCIPITAL POTENTIALS RECORDED FROM SCALP ELECTRODES IN RESPONSE TO FOCAL VISUAL ILLUMINATION. Invest Ophthalmol. 1963 Aug;2:393-406. No abstract available.
• Olmsted ZT, Silverstein JW, Einstein EH, Sowulewski J, Nelson P, Boockvar JA, D'Amico RS. Evolution of flash visual evoked potentials to monitor visual pathway integrity during tumor resection: illustrative cases and literature review. Neurosurg Rev. 2023 Jan 30;46(1):46. doi: 10.1007/s10143-023-01955-z.
• Mariani V, Sartori I, Revay M, Mai R, Lizio D, Berta L, Rizzi M, Cossu M. Intraoperative Corticocortical Evoked Potentials for Language Monitoring in Epilepsy Surgery. World Neurosurg. 2021 Jul;151:e109-e121. doi: 10.1016/j.wneu.2021.03.141. Epub 2021 Apr 2.
• Yamao Y, Suzuki K, Kunieda T, Matsumoto R, Arakawa Y, Nakae T, Nishida S, Inano R, Shibata S, Shimotake A, Kikuchi T, Sawamoto N, Mikuni N, Ikeda A, Fukuyama H, Miyamoto S. Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway. Hum Brain Mapp. 2017 Apr;38(4):1977-1991. doi: 10.1002/hbm.23498. Epub 2017 Jan 23.
• Yamao Y, Matsumoto R, Kunieda T, Arakawa Y, Kobayashi K, Usami K, Shibata S, Kikuchi T, Sawamoto N, Mikuni N, Ikeda A, Fukuyama H, Miyamoto S. Intraoperative dorsal language network mapping by using single-pulse electrical stimulation. Hum Brain Mapp. 2014 Sep;35(9):4345-61. doi: 10.1002/hbm.22479. Epub 2014 Feb 24.
• Suzuki Y, Enatsu R, Kanno A, Yokoyama R, Suzuki H, Tachibana S, Akiyama Y, Mikami T, Ochi S, Yamakage M, Mikuni N. The Influence of Anesthesia on Corticocortical Evoked Potential Monitoring Network Between Frontal and Temporoparietal Cortices. World Neurosurg. 2019 Mar;123:e685-e692. doi: 10.1016/j.wneu.2018.11.253. Epub 2018 Dec 18.
• Seidel K, Wermelinger J, Alvarez-Abut P, Deletis V, Raabe A, Zhang D, Schucht P. Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation. Clin Neurophysiol. 2024 May;161:256-267. doi: 10.1016/j.clinph.2023.12.136. Epub 2024 Mar 5.
• Titov O, Bykanov A, Pitskhelauri D, Danilov G. Neuromonitoring of the language pathways using cortico-cortical evoked potentials: a systematic review and meta-analysis. Neurosurg Rev. 2022 Jun;45(3):1883-1894. doi: 10.1007/s10143-021-01718-8. Epub 2022 Jan 15.
• Saito T, Tamura M, Muragaki Y, Maruyama T, Kubota Y, Fukuchi S, Nitta M, Chernov M, Okamoto S, Sugiyama K, Kurisu K, Sakai KL, Okada Y, Iseki H. Intraoperative cortico-cortical evoked potentials for the evaluation of language function during brain tumor resection: initial experience with 13 cases. J Neurosurg. 2014 Oct;121(4):827-38. doi: 10.3171/2014.4.JNS131195. Epub 2014 May 30.
• Chang EF, Clark A, Smith JS, Polley MY, Chang SM, Barbaro NM, Parsa AT, McDermott MW, Berger MS. Functional mapping-guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival. Clinical article. J Neurosurg. 2011 Mar;114(3):566-73. doi: 10.3171/2010.6.JNS091246. Epub 2010 Jul 16.
• Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. Low-threshold monopolar motor mapping for resection of primary motor cortex tumors. Neurosurgery. 2012 Sep;71(1 Suppl Operative):104-14; discussion 114-5. doi: 10.1227/NEU.0b013e31824c02a0.
• Krieg SM, Shiban E, Droese D, Gempt J, Buchmann N, Pape H, Ryang YM, Meyer B, Ringel F. Predictive value and safety of intraoperative neurophysiological monitoring with motor evoked potentials in glioma surgery. Neurosurgery. 2012 May;70(5):1060-70; discussion 1070-1. doi: 10.1227/NEU.0b013e31823f5ade.
• Schucht P, Seidel K, Jilch A, Beck J, Raabe A. A review of monopolar motor mapping and a comprehensive guide to continuous dynamic motor mapping for resection of motor eloquent brain tumors. Neurochirurgie. 2017 Jun;63(3):175-180. doi: 10.1016/j.neuchi.2017.01.007. Epub 2017 May 13.
• Al-Adli NN, Young JS, Sibih YE, Berger MS. Technical Aspects of Motor and Language Mapping in Glioma Patients. Cancers (Basel). 2023 Apr 6;15(7):2173. doi: 10.3390/cancers15072173.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 12, 2026
• First Submitted That Met QC Criteria: August 24, 2026
• First Posted (Actual): August 27, 2026

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: intraoperative monitoring; visual evoked potential; motor evoked potential; intraoperative neurophysiological monitoring; IOM; cortico-cortical evoked potential; IOM in brain tumor surgery
• Additional Relevant MeSH Terms: Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Monitoring, Physiologic; Monitoring, Intraoperative; Neurophysiological Monitoring; Intraoperative Neurophysiological Monitoring
• Other Study ID Numbers: SDU-2025-176 - (3241)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All project data will be made available through Zenodo open data repository (CERN) after the end of the project. Results will be published in international peer-reviewed Open Access journals and presented at national and international neurosurgical and neurophysiological conferences. Lay summaries will be disseminated through patient organizations, including the Danish Brain Tumor Association, and presented in clinical and regional forums to ensure broad accessibility for both healthcare professionals and the public.

IPD Sharing Time Frame

IPD will be available through Zenodo open data repository after the end of project, which is planned at 31.12.2029, and for at least twenty years.

Study Protocol, Statistical Analysis Plan, and Informed Consent Form will be available at project start on 01.01.2027 through publication of the protocol at the University of Southern Denmark's website, and through publication at clinicaltrials.gov., and will be kept public as long as possible.

• IPD Sharing Access Criteria: All researchers will be able to access the IPD and supporting information, including the project's anonymised outcome measures.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No